EP1087986A1 - 7.alpha.-methyl 19-nortestosterone undecanoate with androgenic activity - Google Patents
7.alpha.-methyl 19-nortestosterone undecanoate with androgenic activityInfo
- Publication number
- EP1087986A1 EP1087986A1 EP99929208A EP99929208A EP1087986A1 EP 1087986 A1 EP1087986 A1 EP 1087986A1 EP 99929208 A EP99929208 A EP 99929208A EP 99929208 A EP99929208 A EP 99929208A EP 1087986 A1 EP1087986 A1 EP 1087986A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- undecanoate
- compound
- testosterone
- androgen
- ment
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 230000001548 androgenic effect Effects 0.000 title description 7
- YSGQGNQWBLYHPE-UHFFFAOYSA-N 17-hydroxy-7,13-dimethyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1CC2(C)C(O)CCC2C2C(C)CC3=CC(=O)CCC3C21 YSGQGNQWBLYHPE-UHFFFAOYSA-N 0.000 title 1
- YSGQGNQWBLYHPE-CFUSNLFHSA-N (7r,8r,9s,10r,13s,14s,17s)-17-hydroxy-7,13-dimethyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1C[C@]2(C)[C@@H](O)CC[C@H]2[C@@H]2[C@H](C)CC3=CC(=O)CC[C@@H]3[C@H]21 YSGQGNQWBLYHPE-CFUSNLFHSA-N 0.000 claims abstract description 27
- 239000003098 androgen Substances 0.000 claims abstract description 27
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- 239000003814 drug Substances 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- JFEPJTGMGDGPHJ-PNKHAZJDSA-N (8r,9s,10r,13s,14s)-13-methyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 JFEPJTGMGDGPHJ-PNKHAZJDSA-N 0.000 claims description 3
- WAHQVRCNDCHDIB-QZYSPNBYSA-N [(3s,8r,9s,10r,13s,14s,17r)-17-acetyl-17-acetyloxy-6,10,13-trimethyl-1,2,3,8,9,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-yl] 3-cyclopentylpropanoate Chemical compound O([C@@H]1C=C2C(C)=C[C@H]3[C@@H]4CC[C@]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)(OC(=O)C)C(C)=O)C(=O)CCC1CCCC1 WAHQVRCNDCHDIB-QZYSPNBYSA-N 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000000583 progesterone congener Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 abstract description 26
- 229960003604 testosterone Drugs 0.000 abstract description 12
- 238000002347 injection Methods 0.000 abstract description 7
- 239000007924 injection Substances 0.000 abstract description 7
- 150000003515 testosterones Chemical class 0.000 abstract description 4
- WRLOOHHQBLTCLM-QKLCDPPYSA-N [(7r,8r,9s,10r,13s,14s,17s)-7,13-dimethyl-3-oxo-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-17-yl] undecanoate Chemical compound C([C@H]1C)C2=CC(=O)CC[C@@H]2[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCCCCCCCC)[C@@]1(C)CC2 WRLOOHHQBLTCLM-QKLCDPPYSA-N 0.000 abstract 1
- 239000003921 oil Substances 0.000 description 11
- 238000000034 method Methods 0.000 description 8
- 239000002775 capsule Substances 0.000 description 6
- 229940088597 hormone Drugs 0.000 description 6
- 239000005556 hormone Substances 0.000 description 6
- 230000003389 potentiating effect Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 229940030486 androgens Drugs 0.000 description 5
- 238000002657 hormone replacement therapy Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 241000220438 Arachis Species 0.000 description 3
- 235000003911 Arachis Nutrition 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
- 108700012941 GNRH1 Proteins 0.000 description 2
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 2
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
- 239000005642 Oleic acid Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 230000002254 contraceptive effect Effects 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- UDSFVOAUHKGBEK-CNQKSJKFSA-N testosterone undecanoate Chemical group C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](OC(=O)CCCCCCCCCC)[C@@]1(C)CC2 UDSFVOAUHKGBEK-CNQKSJKFSA-N 0.000 description 2
- 229960000746 testosterone undecanoate Drugs 0.000 description 2
- MSEZLHAVPJYYIQ-VMXHOPILSA-N (8s,9s,10r,13s,14s)-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 MSEZLHAVPJYYIQ-VMXHOPILSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 235000003846 Ricinus Nutrition 0.000 description 1
- 241000322381 Ricinus <louse> Species 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 229960003473 androstanolone Drugs 0.000 description 1
- 230000002054 antogonadotrophic effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 239000002583 male contraceptive agent Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JUKPJGZUFHCZQI-UHFFFAOYSA-N undecanoyl chloride Chemical compound CCCCCCCCCCC(Cl)=O JUKPJGZUFHCZQI-UHFFFAOYSA-N 0.000 description 1
- 239000012905 visible particle Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0051—Estrane derivatives
- C07J1/0066—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa
- C07J1/007—Estrane derivatives substituted in position 17 beta not substituted in position 17 alfa the substituent being an OH group free esterified or etherified
- C07J1/0074—Esters
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/26—Androgens
Definitions
- the invention is in the field of androgenic hormones, more specifically derivatives of testosterone.
- Testosterone derivatives are known. Testosterone itself, the natural male hormone, has many known drawbacks as far as methods of administration are concerned. It has a short-lasting activity, is insoluble in the usual pharmaceutically acceptable media, and is not very potent. The more potent dihydrotestosterone (5 ⁇ -reduced form of testosterone) is considered a health-risk, notably for the prostate. A somewhat better soluble derivative is testosterone undecanoate, which is known as the active substance in the product Andriol®.
- MENT 7 ⁇ -methyl-19-nortestosterone
- related compounds such as disclosed in FR 4.521 M and US 5,342,834.
- MENT suffers from a bad solubility and short duration of action.
- male contraception may comprise a regimen of administration of hormones in which a progestagen serves to achieve a contraceptive effect and an androgen serves to supplement the resulting decreased testosterone level.
- a progestagen serves to achieve a contraceptive effect
- an androgen serves to supplement the resulting decreased testosterone level.
- male contraception is performed with an androgenic hormone alone.
- the regular androgen intake needed for this requires androgens which are improved as to potency and duration of action, and for which a practical way of administration is available.
- RDP an androgen having an improved relative "dissolved potency", hereinafter referred to as RDP, wherein the RDP of a given androgen in a given medium is the product of its androgenic potency relative to that of the natural male hormone testosterone and its solubility in the medium relative to that of testosterone.
- the invention is the compound (7 ⁇ ,17 ⁇ )-7-methyl-17-[(l- oxoundecyl)oxy]estr-4-en-3-one, which has the following structural formula:
- the compound of the invention is also to be referred to as 7 ⁇ -methyl-19-nortestosterone undecanoate, in short MENT undecanoate.
- the compound of the invention has a significantly better solubility than could be expected on the basis of the known testosterone derivatives. Moreover, the compound of the invention has a surprisingly higher RDP than the known compounds.
- the compound of the invention can be prepared by esterification of the 17-OH group of MENT with undecanoic acid or derivatives thereof. This esterification may be carried out using methods well known in the art or readily available from the chemical literature, for example, using methods and catalysts described in Advanced Organic Chemistry, J. March, 4th Ed, pages 1281-1282, 1992.
- MENT can be prepared as disclosed in FR 4.521 M and US 5,342,834.
- the invention also pertains to the compound MENT undecanoate as a medicine.
- the compound of the invention being a potent androgen, it can be used in, ter alia, male contraception and male or female hormone replacement therapy.
- the invention also pertains to a method of treatment of androgen insufficiency, by administering to a human male or female an effective amount of MENT undecanoate.
- the invention also is in the use of MENT undecanoate for the preparation of a medicine for treating androgen insufficiency.
- the term "androgen insufficiency" is to be understood to pertain to all kinds of diseases, disorders, and symptoms in which a male or a female suffers from too low a testosterone level, such as in hypogonadal men.
- the androgen insufficiency to be treated by the compound of the invention is the reduction of the testosterone level which a human male incurs as a result of age (the compound of the invention is then used for male hormone replacement therapy), or when he is subject to male contraception.
- the compound of the invention especially serves to neutralise the effect of regimens of male hormone contraception in which a sterilitant such as a progestagen or LHRH (luteinizing hormone releasing hormone) is administered regularly, e.g. daily, or it is used as the sole male contraceptive substance.
- the invention also relates to pharmaceutical formulations comprising MENT undecanoate and a pharmaceutically acceptable carrier.
- the carrier may be in a solid form or liquid form
- the formulation may be an oral dosage unit such as a tablet or, preferably, an oral solution, e.g. in a capsule.
- Methods and compositions for making such dosage units are well- known to those skilled in the art. For example, conventional techniques for making tablets and pills, containing active ingredients, are described in the standard reference, Gennaro et al, Remington's Pharmaceutical Sciences, (18th ed., Mack Publishing Company, 1990, see especially Part 8: Pharmaceutical Preparations and Their Manufacture).
- the compound can also be administered via an implant, a patch, or any other suitable device for the sustained release of an androgen composition.
- the preferred oral dosage unit is that of a capsule containing the compound of the invention taken up in a liquid medium as described below.
- administration of the compound dissolved in an oil is preferred, i.e. either orally as above, and notably via (intramuscular) injection.
- MENT undecanoate has a solubility in oily media, which makes it particularly suitable for a liquid pharmaceutical formulation comprising MENT undecanoate dissolved in a pharmaceutically acceptable oil.
- Suitable oils are, e.g., arachis oil, oleic acid, ricinus oil, sesam oil and the like. Arachis oil is preferred.
- the preferred injection device is a needleless injection system, e.g. as described in US 5,599,302.
- the compound may also be suspended in an aqueous medium, but the above solutions in oil are preferred.
- Methods and compositions for making liquids suitable for parenteral administration are known in the art, see e.g. Remington's, pages 1545 ff.
- any capsule made from a pharmaceutically acceptable wall material can be employed.
- Methods and compositions for making capsules suitable for oral administration are known in the art, see e.g. Remington's, pages 1658 ff.
- a preferred material is a softgel such as used for Andriol® capsules.
- the invention also pertains to a method of treatment of androgen insufficiency, by administering to a human male, by injection or by means of an oral dosage unit, an effective amount of MENT undecanoate dissolved in a pharmaceutically acceptable oil.
- the invention also is in the use of MENT undecanoate for the preparation of a medicine for treating androgen insufficiency by injecting into a human male an effective amount of MENT undecanoate dissolved in a pharmaceutically acceptable oil, or by orally administering such an oily solution.
- the dose of and regimen of administration MENT undecanoate, or a pharmaceutical composition thereof, to be administered will obviously depend on the therapeutic effect to be achieved and will vary with the route of administration, and the age and condition of the individual subject to whom the medicament is to be administered, and/or or the particular contraceptive or HRT regimen in which it is used. Typical doses are 100 mg or more per three months upon intramuscular administration and 50-250 mg, more preferably 80 mg per day upon oral administration.
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Endocrinology (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Percussion Or Vibration Massage (AREA)
- Cultivation Receptacles Or Flower-Pots, Or Pots For Seedlings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP99929208A EP1087986B1 (en) | 1998-06-19 | 1999-06-14 | 7.alpha.-methyl 19-nortestosterone undecanoate with androgenic activity |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP98202052 | 1998-06-19 | ||
EP98202052 | 1998-06-19 | ||
EP99929208A EP1087986B1 (en) | 1998-06-19 | 1999-06-14 | 7.alpha.-methyl 19-nortestosterone undecanoate with androgenic activity |
PCT/EP1999/004102 WO1999067271A1 (en) | 1998-06-19 | 1999-06-14 | Testosterone derivative |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1087986A1 true EP1087986A1 (en) | 2001-04-04 |
EP1087986B1 EP1087986B1 (en) | 2002-04-10 |
Family
ID=8233831
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP99929208A Expired - Lifetime EP1087986B1 (en) | 1998-06-19 | 1999-06-14 | 7.alpha.-methyl 19-nortestosterone undecanoate with androgenic activity |
Country Status (26)
Country | Link |
---|---|
US (3) | US6437158B1 (en) |
EP (1) | EP1087986B1 (en) |
JP (1) | JP2002518514A (en) |
KR (1) | KR100596649B1 (en) |
CN (1) | CN1172949C (en) |
AT (1) | ATE215961T1 (en) |
AU (1) | AU756739B2 (en) |
BR (1) | BR9911344A (en) |
CA (1) | CA2333985C (en) |
CZ (1) | CZ293319B6 (en) |
DE (1) | DE69901250T2 (en) |
DK (1) | DK1087986T3 (en) |
ES (1) | ES2175989T3 (en) |
HK (1) | HK1034263A1 (en) |
HU (1) | HUP0102274A3 (en) |
ID (1) | ID27260A (en) |
IL (1) | IL139689A (en) |
NO (1) | NO316518B1 (en) |
NZ (1) | NZ508299A (en) |
PL (1) | PL191285B1 (en) |
PT (1) | PT1087986E (en) |
RU (1) | RU2216546C2 (en) |
SK (1) | SK282796B6 (en) |
TR (1) | TR200003743T2 (en) |
WO (1) | WO1999067271A1 (en) |
ZA (1) | ZA200006813B (en) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ES2204613T3 (en) * | 1999-04-06 | 2004-05-01 | Akzo Nobel N.V. | ANDROGENS 7-ALFA ORALALLY ACTIVE RENT. |
BR0112791A (en) * | 2000-07-28 | 2003-06-24 | Akzo Nobel Nv | 16alpha-substituted steroidal compound, use thereof, treatment methods for selective activation of alpha subtype estrogen receptors, and for hormone replacement therapy or contraception, and, pharmaceutical composition |
JP3774888B2 (en) * | 2001-11-28 | 2006-05-17 | 日本化薬株式会社 | Highly sensitive detection method for steroid compounds by LC-MS |
TW200404552A (en) * | 2002-05-30 | 2004-04-01 | Akzo Nobel Nv | Self administered contraception |
TW200400041A (en) * | 2002-05-30 | 2004-01-01 | Akzo Nobel Nv | Use of new etonogestrel esters |
TW200403065A (en) | 2002-05-30 | 2004-03-01 | Akzo Nobel Nv | New etonogestrel esters |
GB0304927D0 (en) | 2003-03-04 | 2003-04-09 | Resolution Chemicals Ltd | Process for the production of tibolone |
JO2505B1 (en) | 2003-03-14 | 2009-10-05 | باير شيرنغ فارما اكتنجيسيلشافت | method and pharmaceutical compositions for reliable achievements of acceptable serum testosterone levels |
JO2492B1 (en) | 2003-04-28 | 2009-10-05 | شيرينج ايه جي | pharmaceutical composition in the form of a hydrogel for transdermal administration of active ingredients |
PE20050677A1 (en) | 2003-12-22 | 2005-10-04 | Akzo Nobel Nv | STEROIDS WITH ANDROGENIC PROFILE AND MIXED PROGESTAGENIC |
UA89964C2 (en) | 2004-09-08 | 2010-03-25 | Н.В. Органон | 15beta-substituted steroids having selective estrogenic activity |
EP1879382B1 (en) | 2006-07-10 | 2017-09-06 | Samsung Electronics Co., Ltd. | Multi-screen display apparatus and method for digital broadcast receiver |
WO2008101030A1 (en) * | 2007-02-13 | 2008-08-21 | The Regents Of The University Of California | Methods for amplifying steroid hormone effects |
US20090017107A1 (en) * | 2007-07-13 | 2009-01-15 | Oral Delivery Technology Ltd. | Novel composition to increase libido |
US20090018107A1 (en) * | 2007-07-13 | 2009-01-15 | Oral Delivery Technology Ltd. | Novel composition to increase muscle strength |
US20100303937A1 (en) * | 2009-06-01 | 2010-12-02 | Michael Farber | Novel composition to increase testosterone levels |
CN102558267A (en) * | 2012-01-13 | 2012-07-11 | 宜城市共同药业有限公司 | Preparation method of testosterone enanthate |
US9950125B2 (en) * | 2012-04-06 | 2018-04-24 | Antares Pharma, Inc. | Needle assisted jet injection administration of testosterone compositions |
EP4349383A3 (en) | 2013-02-11 | 2024-06-19 | Antares Pharma, Inc. | Needle assisted jet injection device having reduced trigger force |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5342834A (en) * | 1989-04-07 | 1994-08-30 | The Population Council, Inc. | Method for androgen supplementation |
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